Type I interferons are important co-stimulatory signals during T cell receptor mediated human MAIT cell activation
Type I interferons are important co-stimulatory signals during T cell receptor mediated human MAIT cell activation
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DOI：
10.1002/eji.201948279
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发表时间：
2019-11-14
影响因子：
5.4
通讯作者：
Ussher, James E.
中科院分区：
文献类型：
--
作者：
Lamichhane, Rajesh;Galvin, Henry;Ussher, James E.
粘液相关不变T（MAIT）细胞是丰富的非常规T细胞，其可以通过其TCR或先天性细胞因子刺激。MAIT细胞TCR识别与MR 1结合的嘧啶配体，该嘧啶配体来源于核黄素合成细菌。在感染中，细菌不仅提供嘧啶配体，还提供共刺激信号，如TLR激动剂，其可以调节TCR介导的活化。最近，I型干扰素（T1-IFN）已被鉴定为有助于马槟榔碱介导的MAIT细胞活化。然而，T1-IFN在TCR介导的MAIT细胞活化过程中是否也有作用尚不清楚。在这项研究中，我们研究了T1-IFN在TCR介导的MR 1配体5-氨基-6-d-核糖基氨基尿嘧啶/甲基乙二醛活化MAIT细胞过程中的共刺激作用。我们发现，T1-IFN能够促进干扰素-γ和颗粒酶B在5-氨基-6-D-核糖基氨基尿嘧啶/甲基甘氨酸刺激的MAIT细胞的生产。类似地，流感病毒诱导的T1-IFN增强TCR介导的MAIT细胞活化。还证明了T1-IFN在核黄素合成细菌调节MAIT细胞活化中的重要作用。T1-IFN的共刺激作用在肝源性MAIT细胞中也是明显的。T1-IFN直接作用于MAIT细胞以增强它们对TCR刺激的应答。总的来说，我们的研究结果确立了T1-IFN在TCR介导的MAIT细胞活化过程中的重要免疫调节作用。
Mucosal associated invariant T (MAIT) cells are abundant unconventional T cells that can be stimulated either via their TCR or by innate cytokines. The MAIT cell TCR recognises a pyrimidine ligand, derived from riboflavin synthesising bacteria, bound to MR1. In infection, bacteria not only provide the pyrimidine ligand but also co-stimulatory signals, such as TLR agonists, that can modulate TCR-mediated activation. Recently, type I interferons (T1-IFNs) have been identified as contributing to cytokine-mediated MAIT cell activation. However, it is unknown whether T1-IFNs also have a role during TCR-mediated MAIT cell activation. In this study, we investigated the co-stimulatory role of T1-IFNs during TCR-mediated activation of MAIT cells by the MR1 ligand 5-amino-6-d-ribitylaminouracil/methylglyoxal. We found that T1-IFNs were able to boost interferon-gamma and granzyme B production in 5-amino-6-d-ribitylaminouracil/methylglyoxal-stimulated MAIT cells. Similarly, influenza virus-induced T1-IFNs enhanced TCR-mediated MAIT cell activation. An essential role of T1-IFNs in regulating MAIT cell activation by riboflavin synthesising bacteria was also demonstrated. The co-stimulatory role of T1-IFNs was also evident in liver-derived MAIT cells. T1-IFNs acted directly on MAIT cells to enhance their response to TCR stimulation. Overall, our findings establish an important immunomodulatory role of T1-IFNs during TCR-mediated MAIT cell activation.